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¹H NMR based serum metabolic profiles associated with pathological progression of pancreatic islet β cell tumor in Rip1-Tag2 mice.

Yang Y, Liu Y, Zheng L, Zhang Q, Gu Q, Wang L, Wang L - Int. J. Biol. Sci. (2015)

Bottom Line: Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells.In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism.The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Basic Course, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China ; 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.

ABSTRACT
Pancreatic islet β cell tumor is the most common islet cell tumor. A well-characterized tumor progression in Rip1-Tag2 mice undergoes five stages, involving normal, hyperplasia, angiogenic islets, tumorigenesis and invasive carcinoma. (1)H NMR based metabonomics was applied to identify potential biomarkers for monitoring pancreatic islet β cell tumor progression in Rip1-Tag2 mice. Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells. At angiogenic islets stage, the up-regulated glycolysis, disturbed choline and phospholipid metabolism composed the metabolic signature. In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism. All the changes were aggravated at invasive carcinoma stage, coupled with notable changes in alanine, glutamate and glycine. Moreover, the distinct metabolic phenotype was found associated with the implanting of SV40 large T antigen in Rip1-Tag2 mice. The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

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PCA Scores plot of sera 1H NMR data in Rip1-Tag2 mice at different pathological stage (R2=82.8%, Q2=79.3%). 3 weeks (●), 5 weeks (●), 8 weeks (◆), 10 weeks (■) and 14 weeks (▲).
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Figure 4: PCA Scores plot of sera 1H NMR data in Rip1-Tag2 mice at different pathological stage (R2=82.8%, Q2=79.3%). 3 weeks (●), 5 weeks (●), 8 weeks (◆), 10 weeks (■) and 14 weeks (▲).

Mentions: The PCA model was constructed to classify the Rip1-Tag2 sera samples at different stages. In Fig. 4, an obvious distribution trajectory was displayed with R2 of 82.8% and Q2 of 79.3% as the arrow showed. It was noted that there was serious overlapping between the samples at 3 weeks and 5 weeks. By looking at the 1H spectra of these two groups, we speculated that this distribution pattern came from the similarity in 1H spectra profiles. This original differentiation tendency demonstrated the dynamic metabolic variations correlated with the development of pancreatic islet β cell carcinoma. Therefore, the serum metabolic characteristics reveal the metabonomic perturbations along with the pathological progress.


¹H NMR based serum metabolic profiles associated with pathological progression of pancreatic islet β cell tumor in Rip1-Tag2 mice.

Yang Y, Liu Y, Zheng L, Zhang Q, Gu Q, Wang L, Wang L - Int. J. Biol. Sci. (2015)

PCA Scores plot of sera 1H NMR data in Rip1-Tag2 mice at different pathological stage (R2=82.8%, Q2=79.3%). 3 weeks (●), 5 weeks (●), 8 weeks (◆), 10 weeks (■) and 14 weeks (▲).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4400390&req=5

Figure 4: PCA Scores plot of sera 1H NMR data in Rip1-Tag2 mice at different pathological stage (R2=82.8%, Q2=79.3%). 3 weeks (●), 5 weeks (●), 8 weeks (◆), 10 weeks (■) and 14 weeks (▲).
Mentions: The PCA model was constructed to classify the Rip1-Tag2 sera samples at different stages. In Fig. 4, an obvious distribution trajectory was displayed with R2 of 82.8% and Q2 of 79.3% as the arrow showed. It was noted that there was serious overlapping between the samples at 3 weeks and 5 weeks. By looking at the 1H spectra of these two groups, we speculated that this distribution pattern came from the similarity in 1H spectra profiles. This original differentiation tendency demonstrated the dynamic metabolic variations correlated with the development of pancreatic islet β cell carcinoma. Therefore, the serum metabolic characteristics reveal the metabonomic perturbations along with the pathological progress.

Bottom Line: Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells.In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism.The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Basic Course, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China ; 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.

ABSTRACT
Pancreatic islet β cell tumor is the most common islet cell tumor. A well-characterized tumor progression in Rip1-Tag2 mice undergoes five stages, involving normal, hyperplasia, angiogenic islets, tumorigenesis and invasive carcinoma. (1)H NMR based metabonomics was applied to identify potential biomarkers for monitoring pancreatic islet β cell tumor progression in Rip1-Tag2 mice. Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells. At angiogenic islets stage, the up-regulated glycolysis, disturbed choline and phospholipid metabolism composed the metabolic signature. In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism. All the changes were aggravated at invasive carcinoma stage, coupled with notable changes in alanine, glutamate and glycine. Moreover, the distinct metabolic phenotype was found associated with the implanting of SV40 large T antigen in Rip1-Tag2 mice. The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

Show MeSH
Related in: MedlinePlus